Hotchkiss R S, Swanson P E, Freeman B D, Tinsley K W, Cobb J P, Matuschak G M, Buchman T G, Karl I E
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Crit Care Med. 1999 Jul;27(7):1230-51. doi: 10.1097/00003246-199907000-00002.
The purpose of this study was to determine whether apoptosis is a major mechanism of cell death in patients with sepsis. The activities of caspase-3 and the antiapoptotic protein, BCL-2, were investigated also.
A prospective study of 20 patients who died of sepsis and multiple organ dysfunction was performed. The control group of 16 patients consisted of critically ill, nonseptic patients who were evaluated either prospectively (7) or retrospectively (9). In addition, normal colon sections from seven patients who had bowel resections were included. Apoptosis was evaluated in hematoxylin and eosin-stained specimens by deoxyuridine triphosphate nick end-labeling (TUNEL) and by DNA gel electrophoresis.
Two academic medical centers.
Critically ill patients.
In septic patients, apoptosis was detected in diverse organs by all three methods with a predominance in lymphocytes and intestinal epithelial cells. Hematoxylin and eosin-stained specimens from septic patients demonstrated at least focal apoptosis in 56.3% of spleens, 47.1% of colons, and 27.7% of ileums. Indirect evidence of lymphocyte apoptosis in septic patients included extensive depletion of lymphocytes in white pulp and a marked lymphocytopenia in 15 of 19 patients. Hematoxylin and eosin from nonseptic patients' tissues revealed a low level of apoptosis in one patient only. The TUNEL method increased in positivity with a delay in tissue fixation and was highly positive in many tissues from both septic and nonseptic patients. Immunohistochemical staining for active caspase-3 showed a marked increase in septic vs. nonseptic patients (p < .01), with >25% to 50% of cells being positive focally in the splenic white pulp of six septic but in no nonseptic patients.
We conclude that caspase-3-mediated apoptosis causes extensive lymphocyte apoptosis in sepsis and may contribute to the impaired immune response that characterizes the disorder.
本研究旨在确定凋亡是否为脓毒症患者细胞死亡的主要机制。同时还研究了半胱天冬酶 -3和抗凋亡蛋白BCL-2的活性。
对20例死于脓毒症和多器官功能障碍的患者进行了前瞻性研究。16例患者的对照组由病情危重的非脓毒症患者组成，其中7例为前瞻性评估，9例为回顾性评估。此外，纳入了7例行肠切除术患者的正常结肠切片。通过脱氧尿苷三磷酸缺口末端标记法（TUNEL）和DNA凝胶电泳，在苏木精和伊红染色的标本中评估凋亡情况。
两个学术医学中心。
病情危重的患者。
在脓毒症患者中，通过所有三种方法均在多种器官中检测到凋亡，以淋巴细胞和肠上皮细胞为主。脓毒症患者苏木精和伊红染色的标本显示，至少56.3%的脾脏、47.1%的结肠和27.7%的回肠存在局灶性凋亡。脓毒症患者淋巴细胞凋亡的间接证据包括白髓中淋巴细胞广泛耗竭，19例患者中有15例出现明显淋巴细胞减少。非脓毒症患者组织的苏木精和伊红染色仅在1例患者中显示低水平凋亡。TUNEL法的阳性率随组织固定延迟而增加，在脓毒症和非脓毒症患者的许多组织中均呈高度阳性。活性半胱天冬酶 -3的免疫组化染色显示，脓毒症患者与非脓毒症患者相比显著增加（p <.01），6例脓毒症患者的脾白髓中有>25%至50%的细胞局灶性阳性，而非脓毒症患者中无此情况。
我们得出结论，半胱天冬酶 -3介导的凋亡导致脓毒症中广泛的淋巴细胞凋亡，并可能导致该疾病特征性的免疫反应受损。
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